1. Field of the Invention
This invention relates to a novel chondromodulin protein. More particularly, it relates to chondromodulin-II protein capable of stimulating the growth of chondrocytes in the presence or absence of fibroblast growth factor and promoting the differential potency of said cells, and a pharmaceutical composition containing said protein as an active ingredient.
2. Description of Related Art
Almost all the bones of mammals, except for the flat bones such as cranial bone and the like, are formed through a mechanism called "intracartilaginous ossification", which comprises expression of primordial chondrocytes during the embryonic stage, growth and differentiation of said cartilaginous cells, generation of primordial cartilages such as proteoglycan, collagen II, collagen IX collagen X and the like, infiltration of capillary vessels which is accompanied by the decomposition of ground substance of cartilage and progression of calcification around the vesicles of said ground substance, and the replacement thereof with bone as the final step. Thus, the cartilage metabolism plays a significantly important role in the bone-formation, especially in the elongation of a bone along the axis.
It has been known that a variety of hormones and growth factors participate in the bone-formation (osteogenesis) process, including insulin-like growth factor (IGF1, IGF2), fibroblast growth factor (FGF), growth hormone, tumor cell growth factor (TGF-.beta.) and the like. It has also been suggested that a certain active factor exists in cartilage, which stimulates the growth and differentiation of chondrocytes. Neam et al. [Peter J. Neam et al., Journal of Biological Chemistry Vol.265, No.17, 9628-9633, (1990)] reported that they separated from No.17, 9628-9633 bovine cartilage a sugar protein having a molecular weight of 18,000 dalton during the study for the identification of constitutive proteins in cartilage. However, they still have not elucidated the biological functions of said sugar protein.
The expression of the growth and differentiation of chondrocytes plays an important role in the course of recovery from fracture or various cartilage diseases as follows: inflammatory reaction at the injured site, growth of the periost-derived cells, expression and growth of chondrocytes, synthesis of extra-cellular ground substances, calcification of said substances, and replacement thereof with bone tissues. As can be easily understood, the growth of cartilage tissue at the site of fracture is essential for the formation of bone tissue. Additionally, it is obvious that the growth of the chondrocytes is also important for the recovery from cartilage diseases accompanied by cartilage destruction or injury. However, there have not been provided any substance which can stimulate the growth of chondrocytes, such substance thereby being useful as an active ingredient for the treatment of the above-mentioned diseases or disorders.